Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany.
International Graduate Program Medical Neurosciences, Charité Universitätsmedizin Berlin, Germany.
Sci Rep. 2016 Dec 15;6:39145. doi: 10.1038/srep39145.
The dopamine transporter (DAT) plays a pivotal role in maintaining optimal dopamine signaling. DAT-overactivity has been linked to various neuropsychiatric disorders yet so far the direct pathological consequences of it has not been fully assessed. We here generated a transgenic rat model that via pronuclear microinjection overexpresses the DAT gene. Our results demonstrate that DAT-overexpression induces multiple neurobiological effects that exceeded the expected alterations in the corticostriatal dopamine system. Furthermore, transgenic rats specifically exhibited behavioral and pharmaco-therapeutic profiles phenotypic of repetitive disorders. Together our findings suggest that the DAT rat model will constitute a valuable tool for further investigations into the pathological influence of DAT overexpression on neural systems relevant to neuropsychiatric disorders.
多巴胺转运体(DAT)在维持最佳多巴胺信号中起着关键作用。DAT 过度活跃与各种神经精神疾病有关,但迄今为止,其直接的病理后果尚未得到充分评估。我们在这里通过原核显微注射生成了一种转基因大鼠模型,该模型过度表达 DAT 基因。我们的结果表明,DAT 过表达诱导了多种神经生物学效应,超过了皮质纹状体多巴胺系统中预期的改变。此外,转基因大鼠特别表现出与重复性疾病相关的行为和药物治疗特征。总之,我们的研究结果表明,DAT 大鼠模型将成为进一步研究 DAT 过表达对神经精神疾病相关神经系统的病理影响的有力工具。